Phase I study of oral S-1 plus Cisplatin with concurrent radiotherapy for locally advanced non-small-cell lung cancer.
OBJECTIVE
To determine the maximum tolerated dose (MTD) and recommended dose (RD) of S-1 in combination with cisplatin and thoracic radiotherapy in patients with unresectable Stage III non-small-cell lung cancer (NSCLC).


METHODS
S-1 was administered orally twice daily for 14 days and cisplatin on Days 1 and 8 of each cycle; this was repeated every 3 weeks. Doses of each drug were planned as follows: level 0, 50/40; level 1, 60/40; level 2, 70/40; level 3, 80/40 (S-1 [mg/m(-2)/day(-1)]/cisplatin [mg/m(-2)/day(-1)]). Thoracic radiation therapy was administered in 2 Gy fractions five times weekly to a total dose of 60 Gy.


RESULTS
Ten patients were enrolled in this study. All patients received 60 Gy of thoracic radiotherapy and 7 (70%) patients received four cycles of chemotherapy. At level 1, 2 of 3 patients experienced a delay exceeding 10 days in the cisplatin administration of Day 29. Grade 4 neutropenia and Grade 3 fever occurred in 1 and 1 patients, respectively. Nonhematologic toxicities were mild. None developed >or=Grade 3 esophagitis or lung toxicity. At level 0, 2 of 7 patients developed dose-limiting toxicity. Thus, level 1 was considered the MTD and Level 0 was selected as the RD. Objective responses were seen in all patients.


CONCLUSIONS
The RD is the level 0 dose, and this regimen is a feasible and well-tolerated regimen for the treatment of patients with Stage III NSCLC.
Kaira
Kyoichi
K
Department of Medicine and Molecular Science, Gunma University Graduate School of Medicine, Maebashi, Gunma, Japan. kkaira1970@yahoo.co.jp
Sunaga
Noriaki
N
Yanagitani
Noriko
N
Kawata
Tadayoshi
T
Utsugi
Mitsuyoshi
M
Shimizu
Kimihiro
K
Ebara
Takeshi
T
Kawamura
Hidemasa
H
Nonaka
Tetsuo
T
Ishikawa
Hitoshi
H
Sakurai
Hideyuki
H
Suga
Tatsuo
T
Hara
Kenichiro
K
Hisada
Takeshi
T
Ishizuka
Tamotsu
T
Nakano
Takashi
T
Mori
Masatomo
M
D000284:Administration, Oral; D000368:Aged; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000008:administration & dosage* / Q000009:adverse effects; D002289:Carcinoma, Non-Small-Cell Lung / Q000188:drug therapy* / Q000473:pathology / Q000532:radiotherapy*; D002945:Cisplatin / Q000008:administration & dosage / Q000009:adverse effects; D003131:Combined Modality Therapy; D019583:Dose Fractionation, Radiation; D004334:Drug Administration Schedule; D004338:Drug Combinations; D005260:Female; D006801:Humans; D008175:Lung Neoplasms / Q000188:drug therapy* / Q000473:pathology / Q000532:radiotherapy*; D008297:Male; D020714:Maximum Tolerated Dose; D008875:Middle Aged; D010094:Oxonic Acid / Q000008:administration & dosage / Q000009:adverse effects; D005641:Tegafur / Q000008:administration & dosage / Q000009:adverse effects
D004338:Drug Combinations; C079198:S 1 (combination); D005641:Tegafur; D010094:Oxonic Acid; D002945:Cisplatin